Na+-Glucose Cotransporter Inhibitors as Antidiabetic Agents. III. Synthesis and Pharmacological Properties of 4'-Dehydroxyphlorizin Derivatives Modified at the OH Groups of the Glucose Moiety.

Inhibition of intestinal glucose absorption by anti-diabetic medicinal plants derived from the James Bay Cree traditional pharmacopeia

“…Its clinical applications are limited because phlorizin is less effective if administered orally probably due to intestinal hydrolysis by ␤-glucosidase (Malathi and Crane, 1969;Tsujihara et al, 1996). Phlorizin derivatives have been synthesized and tested as SGLT1 inhibitors (Hongu et al, 1998;Tsujihara et al, 1999;Castaneda et al, 2007). Removal of the glucose moiety from phlorizin yields phloretin (Ehrenkranz et al, 2005).…”

Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for New Anti-Diabetic Agent

“…The most potent compound (3) is anticipated to be hydrolyzed by -glucosidase in the digestive tract. Modification of the OH groups on the glucose moiety was carried out to enhance the resistance against hydrolysis by -glucosidase in the intestine and thus to increase the activity [33]. Among prodrugs of (3), three compounds were more potent than (3) in oral activity: triacetyl (6´-OH on the B ring and 2-, 3-OH on the glucose moiety), 6-O-methoxycarbonyl (4) and 4-Omethoxycarbonyl derivatives.…”

Sodium-dependent glucose transporter protein as a potential therapeutic target for improving glycemic control in diabetes

“…SGLT proteins were first postulated as a possible therapeutic target for the control of blood glucose levels in 1996 by Tsujihara et al 5 These investigators, along with Hongu et al, described the possibility of using SGLT inhibitors as antidiabetic agents on the basis of experimental studies in rats. [5][6][7] Since then, regulation of glucose disposal through SGLT proteins has been considered an important biological target that can be used for the development of innovative therapies to effectively manage diabetes and prevent its long-term complications. 8 The objective of this manuscript is to review the role of SGLT proteins in the pathophysiology of diabetes and to describe the mechanisms by which these transporters may be used for glycemic control and treatment of diabetes.…”